Differentiating keratinocytes express a novel cytochrome P450 enzyme, CYP2b19, having arachidonate monooxygenase activity

Diane S. Keeney, Colin Skinner, Jeffrey Travers, Jorge H. Capdevila, Lillian B. Nanney, Lloyd E. King, Michael R. Waterman

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

The novel cytochrome P450, CYP2B19, is a specific cellular marker of late differentiation in skin keratinocytes. CYP2B19 was discovered in fetal mouse skin where its onset of expression coincides spatially (upper cell layer) and temporally (day 15.5) with the appearance of loricrin-expressing keratinocytes during the stratification stage of fetal epidermis. CYP2B19 is also present postnatally in the differentiated keratinocytes of the epidermis, sebaceous glands, and hair follicles. CYP2B19 mRNA is tightly coupled to the differentiated (granular cell) keratinocyte phenotype in vivo and in vitro. In primary mouse epidermal keratinocytes, it is specifically up-regulated and correlated temporally with calcium-induced differentiation and expression of the late differentiation genes loricrin and profilaggrin. Recombinant CYP2B19 metabolizes arachidonic acid and generates 14,15- and 11,12-epoxyeicosatrienoic (EET) acids, and 11-, 12-, and 15- hydroxyeicosatetraenoic (HETE) acids (20, 35, 18, 7, and 7% of total metabolites, respectively). Arachidonic acid metabolism was stereoselective for 11S, 12R- and 14S,15R-EET, and 11S-, 12R-, and 15R-HETE. The CYP2B19 metabolites 11,12-and 14,15-EET are endogenous constituents of murine epidermis and are present in similar proportions to that generated by the enzyme in vitro, suggesting that CYP2B19 might be the primary enzymatic source of these EETs in murine epidermis.

Original languageEnglish
Pages (from-to)32071-32079
Number of pages9
JournalJournal of Biological Chemistry
Volume273
Issue number48
DOIs
StatePublished - Nov 27 1999

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Mixed Function Oxygenases
Keratinocytes
Cytochrome P-450 Enzyme System
Epidermis
Metabolites
Arachidonic Acid
Skin
Sebaceous Glands
Hair Follicle
Differentiation Antigens
Metabolism
Genes
Cells
Calcium
Phenotype
Messenger RNA
Enzymes
In Vitro Techniques
loricrin

ASJC Scopus subject areas

  • Biochemistry

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Differentiating keratinocytes express a novel cytochrome P450 enzyme, CYP2b19, having arachidonate monooxygenase activity. / Keeney, Diane S.; Skinner, Colin; Travers, Jeffrey; Capdevila, Jorge H.; Nanney, Lillian B.; King, Lloyd E.; Waterman, Michael R.

In: Journal of Biological Chemistry, Vol. 273, No. 48, 27.11.1999, p. 32071-32079.

Research output: Contribution to journalArticle

Keeney, Diane S. ; Skinner, Colin ; Travers, Jeffrey ; Capdevila, Jorge H. ; Nanney, Lillian B. ; King, Lloyd E. ; Waterman, Michael R. / Differentiating keratinocytes express a novel cytochrome P450 enzyme, CYP2b19, having arachidonate monooxygenase activity. In: Journal of Biological Chemistry. 1999 ; Vol. 273, No. 48. pp. 32071-32079.
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